DIGITAL SENSOR WITH REFERENCE CANTILEVER FOR CONVERTING CHEMICAL AND/OR BIOCHEMICAL INFORMATION

Abstract

A sensor is provided for converting chemical and/or biochemical information about an analyte in a sample into an electrical signal. The sensor includes a test cantilever having a base and a deformable part of which a receptor layer is applied thereon for selective reception of an analyte of the sample. Moreover, on the base a passive test transducer is arranged and on the deformable part an active test transducer is arranged. The sensor further includes a reference cantilever having a base and a deformable part on which a reference layer is applied for selective non-reception of the analyte. Moreover, on the base a passive reference transducer is arranged and on the deformable part an active reference transducer is arranged.

Claims

1. A sensor for converting at least one of chemical and biochemical information about an analyte in a sample into an electrical signal, the sensor comprising a test cantilever having a base and a deformable part on which a receptor layer for selective reception of the analyte is applied, where a passive test transducer is arranged on the base and an active test transducer is arranged on the deformable part; a reference cantilever having a base and a deformable part on which a reference layer for selective non-reception of the analyte is applied, where a passive reference transducer is arranged on the base and an active reference transducer is arranged on the deformable part, wherein the active and passive reference transducers and the active and passive test transducers are configured to output an electrical signal corresponding to at least one of an incidence, a concentration and an amount of the analyte in the sample.

2. The sensor according to claim 1, wherein the transducers are each configured to determine an alteration in a surface stress of the reference cantilever and of the test cantilever.

3. The sensor according to claim 1, wherein the transducers are each configured to determine at least one of a deformation and an alteration in a surface stress of the respective deformable parts of the reference cantilever and of the test cantilever, and wherein the changes in at least one of the surface stress and a forces (F) exerted during deformation on each respective base and the deformable parts the reference cantilever and of the test cantilever are detected.

4. The sensor according to claim 3, wherein the force (F) to be detected is at least one of a bending force, a stretching force, a shearing force and a surface stress, or is due to an elasticity modulus of the reference and test cantilevers.

5. The sensor according to claim 3, wherein an effect on the test cantilever caused by the selective reception of the analyte is concluded through a comparison of the deformations, forces and/or surface stresses detected by the transducers.

6. The sensor according to claim 1, wherein the deformable parts of the reference and test cantilevers have identical geometric dimensions, and respective widths of the deformable part of the reference and test cantilevers corresponds to respective lengths of the deformable part of the reference and test cantilevers.

7. The sensor according to claim 1, wherein the respective bases of each of the reference and test cantilevers are arranged as a single base.

8. The sensor according to claim 1, wherein the reference and test cantilevers comprise at least one of Si3N4, SiO2, Si3N4/SiO2, SiC, Si or comprise a polymer.

9. The sensor according to claim 1, wherein the respective transducers have identical intrinsic physical properties and are configured to adapt electrical properties in accordance with forces acting on the reference and test cantilevers.

10. The sensor according to claim 1, wherein a distance (A) between the active reference transducer or test transducer and the passive reference transducer or test transducer is less than 100 μm.

11. The sensor according to claim 1, further comprising electrodes that are configured to electrically contact the respective transducers.

12. The sensor according to claim 11, wherein the transducers are electrically interconnected in a full bridge that is configured to develop a transverse bridge voltage (VB) based on the electrical properties of the transducers.

13. The sensor according to claim 12, further comprising a transverse bridge voltage detector that is configured to detect the transverse bridge voltage (VB) of the full bridge, wherein an incidence of the analyte selectively received by the receptor layer is concluded through the detected transverse bridge voltage (VB).

14. The sensor according to claim 1, wherein electrical properties of the transducers are output via an A/D converter, and an A/D converter logic unit is configured to provide at least one of a differential measurement and an absolute measurement of bending states.

15. The sensor according to claim 14, wherein the sensor is embodied on a chip and a multiplicity of cantilever pairs are arranged on the chip, wherein the A/D converter logic unit is configured to provide signal multiplexing of the measurement signals.

16. The sensor according to claim 1, further comprising: an activation layer configured to activate upper surfaces of the reference and test cantilevers, wherein the activation layer is configured to provide a greater surface stress in comparison to a non-activated lower surface of the reference and test cantilevers, and wherein the activation layer comprises gold.

17. The sensor according to claim 1, further comprising: a passivation layer that passivates lower surfaces of the reference and test cantilevers, wherein the passivation layer is configured to minimize an unspecific protein adhesion on the reference and test cantilevers, and wherein the passivation layer comprises at least one of trimethoxysilane and a blocking substance.

18. The sensor according to claim 1, wherein the reference and test cantilevers each comprise a self-assembling monolayer.

19. The sensor according to claim 1, wherein the receptor layer comprises antibodies for an antigen, and the reference layer comprises an antigen-specific isotype control antibody according to the antibody of the reference layer.

20. The sensor according to claim 1, wherein: the receptor layer provides molecule-specific binding forces and the reference layer provides no binding forces molecule-specifically, or the receptor layer comprises single-strand DNA (ssDNA) and/or other DNA fragments which binds specifically to DNA fragments in the sample, and the reference layer comprises single-strand DNA and/or other DNA fragments which does not bind to any chemical and/or biochemical and/or physical species in the sample but in characteristic parameters coincides with the receptor layer, or the receptor layer comprises single-strand RNA and/or other RNA fragments which binds specifically to RNA fragments in the sample, and the reference layer comprises single-strand RNA and/or other RNA fragments which does not bind to any chemical and/or biochemical and/or physical species in the sample but in characteristic parameters coincides with the receptor layer, or the receptor layer comprises antibodies and/or other and/or further proteins which are able to specifically bind target proteins, and the reference layer comprises specific isotype control antibodies and/or other and/or further proteins which do not bind to any chemical and/or biochemical and/or physical species in the sample, or the receptor layer comprises scFv antibodies and the reference layer comprises scFV antibody-specific isotype control antibodies; or the receptor layer comprises Sars-CoV2 antibodies and the reference layer comprises Sars-CoV2 specific isotype control antibodies; or the receptor layer and the reference layer comprise hydrogels.

21. The sensor according to claim 2, wherein at least one of the deformation and the alteration in the surface stress is achieved in a transverse direction of at least one of the test cantilever and the reference cantilever, wherein the transverse direction runs parallel to the base of at least one of the test cantilever and the reference cantilever.

22. The sensor according to claim 2, wherein at least one of the deformation and the alteration in the surface stress is achieved in a longitudinal direction of at least one of the test cantilever and the reference cantilever, where the longitudinal direction runs perpendicular to the base of at least one of the test cantilever and of the reference cantilever.

Description

BRIEF DESCRIPTION OF THE FIGURES

[0171] Preferred further embodiments of the invention are elucidated in more detail below by the following description of the figures, in which:

[0172] FIG. 1 shows a schematic representation of a first embodiment of the sensor;

[0173] FIGS. 2A, B, C, D show a schematic representation of the cantilevers;

[0174] FIGS. 3A, B show a schematic representation of a second embodiment of the sensor;

[0175] FIG. 4 shows a schematic representation of a third embodiment of the sensor;

[0176] FIGS. 5A, B, C show further schematic representations of further embodiments of the sensor, and a circuit diagram of a full bridge;

[0177] FIG. 6 shows a schematic representation of a chip having multiple cantilever pairs; and

[0178] FIG. 7 shows a schematic representation of the binding of antigens to antibodies.

DETAILED DESCRIPTION OF EXEMPLARY EMBODIMENTS

[0179] In the following, preferred embodiments are described with reference to the figures. Here, elements that are identical, similar or have the same effect are provided with identical reference signs in the various figures, and in some cases a repeated description of these elements is omitted in order to prevent redundancies.

[0180] FIG. 1 schematically shows a first embodiment of the sensor 1 of the invention for converting chemical and/or biochemical information. The sensor 1 comprises a test cantilever 2, which has a base 20 and a deformable part 22. Arranged on the base 20 is a passive test transducer 200, whereas an active test transducer 220 is arranged on the deformable part 22. In analogy to this, the sensor 1 also has a reference cantilever 3, which in turn has a base 30 with a passive reference transducer 300, and a deformable part 32 which has an active reference transducer 320.

[0181] The transducers 200, 220, 300, 320 are each connected via electrodes 40 to an electronic unit 4 which is capable of recording or transmitting a measurement signal from the transducers 200, 220, 300, 320, while the electronic unit 4 is likewise capable of supplying the transducers 200, 220, 300, 320 with current and/or voltage.

[0182] The function of the sensor 1 is to indicate the incidence and preferably the amount of the incidence of an analyte 90 in a sample 9. In FIG. 1 the sample 9 is a fluid produced, for example, by treatment of a swab, more particularly a nasal swab or throat swab, from a test subject. It may also be the case, however, that the sample 9 is saliva or blood or another bodily fluid. It may also be the case, however, that the sample 9 is a gargling fluid that the test subject has gargled. It may also be the case that the sample 9 has been synthesized and/or obtained from a tissue sample or from another substance taken from the test subject. The analyte 90 in this case may be in solution in the sample, or may be present in undissolved form as a suspension or dispersion or emulsion.

[0183] In any case, the aim with the sensor 1 is to investigate the sample 9 for the incidence and/or concentration and/or amount of the analyte 90. For this purpose, a receptor layer 24 is applied on the test cantilever, and an analyte 90 is able to interact with this layer, or a receptor layer 24 is applied which is able to adsorb or absorb the analyte 90. In the case of adsorption, the analyte 90 would adhere on the surface of the receptor layer 24, while in the case of absorption the analyte 90 would penetrate the interior of the reference coating 90.

[0184] When the sample 9 contains an analyte 90, then, the latter is able to interact with the receptor layer 24. This may result in a change in the surface stress of that portion of the deformable part 22 of the test cantilever 2 that is coated with the receptor layer 24, so leading to a deformation of the deformable part 22 of the test cantilever 2. The active test transducer 220 therefore registers a deformation and/or alteration in the surface stress of the deformable part of the test cantilever 2, which is interpreted in turn in the electronic unit 4 as a measurement signal.

[0185] However, because of the interaction with the sample fluid 9, there may already be a deformation recorded by the active test transducer 220, for example by only the surface stress of the fluid acting on the deformable part 22 of the test cantilever 2 and causing it to deform. For a deformation of this kind, accordingly, it is not the presence of an analyte 90 that is responsible.

[0186] In order to establish the magnitude of this basic action of the sample 9 on the test cantilever 2, the reference cantilever 3 is contacted with the sample 9 at the same time as the test cantilever 2. For this purpose the reference cantilever 3 has a reference layer 34, with which an analyte 90 cannot interact, or a reference layer 24 which is unable to adsorb or absorb the analyte 90. In this case interaction with the analyte 90 is to be avoided, in order to enable differentiation relative to the measurement signal from the test cantilever 2.

[0187] With both the test cantilever 2 and the reference cantilever 3 interacting with the sample 9, the two cantilevers 2, 3 interact similarly with the sample 9. The difference in this case, however, is that the test cantilever 2 is additionally able to interact with any analyte 90 that is present, via its reference layer 24. Accordingly, the measurement signals from the active transducers 220, 320 differ if there is an analyte 90 in the sample 9. From the magnitude of the difference between the measurement signals, accordingly, it is possible in the simplest case to infer the amount of the incidence of the analyte 90 in the sample 9.

[0188] The test cantilever 2 and the reference cantilever 3 measure the incidence of the analyte 19 in the sample 9 at different positions, however. At different positions of the sample there may be different ambient conditions, such as, for example, temperature fluctuations or concentration gradients, etc.

[0189] These different ambient conditions can be measured with the passive transducers 200, 300. The passive transducers 200, 300 are arranged on the base and preferably do not detect any measurement signal in the case of a deformation of the deformable part 22, 32 of the reference or test cantilevers 2, 3 respectively. However, the base level of the measurement signal from the passive transducers 200, 300 may be influenced because of these different ambient conditions. By provision, for each measurement value of the active transducers 220, 320 via the passive transducers 200, 300, of a comparative value which looks at the ambient conditions in isolation, it is possible for the influence of the ambient conditions on the measurement signals from the active transducers 220, 320 to be determined and reduced and/or factored out or isolated.

[0190] The sensor 1 can be used accordingly to analyze the incidence of an analyte 90 in a sample 9 in isolation, by reducing and isolating the influence of interactions for which the analyte 90 is not held responsible, by means of a multiplicity of measurement points on the reference and test cantilevers 3, 2. This allows a high measurement accuracy of the incidence of the analyte 90 in the sample 9.

[0191] FIG. 2A shows the comparison of the deformable parts 32, 22 of the reference and test cantilevers 3, 2 in the event of a deformation and longitudinal stretching. The deformable part 32 of the reference cantilever 3 has an upper surface 360 and a lower surface 362. The deformable part 22 of the test cantilever 2 also has an upper surface 260 and a lower surface 262. Where an analyte 90 of the sample 9 interacts with the test cantilever 2 or with the receptor layer 24, there is a deformation of the deformable part 22 from the stationary part (which transitions into the base of the test cantilever) toward the freely movable part of the deformable part 22. The deflection L that is shown is a result in this case of the relative deflection between the deformable part 32 of the reference cantilever 3 and the deformable part 22 of the test cantilever 2, owing to the interaction with the analyte 90.

[0192] The deformation of the deformable part 22 of the test cantilever 2 is shown in FIG. 2B. The cause of this is that the upper surface 260 and the lower surface 262 of the test cantilever 2 stretch to different extents. Because of the large stretching D at the upper surface 260, an active transducer 220 applied thereon may register a stretching force F. The stretching force F registered may in this case be converted by the active transducer 220 into an electronic signal and/or may influence an existing electronics signal, such as an applied voltage, for example. This may be accomplished, for example, by the transducer changing the resistance if it experiences a stretching force F, resulting in turn in a stretching of the transducer 220.

[0193] The transducer could also detect a contraction of the surface on which it is arranged. In the embodiments shown, however, the transducers are always arranged on surfaces for which stretching is anticipated.

[0194] The stretching and/or alteration of surface stress and/or force that is detected by the transducer may alternatively be a bending force or a shearing force or may be caused by a bending force or shearing force or may generally be due to the elasticity modulus of the respective cantilever. In particular, as a result of the securement of the deformable part 22, 32 on the base 20, 30, the deformable part 22, 32, due to an action of force, is oriented along a bending curve by an alteration in the surface stress of the test cantilever. The resulting bending curve is a product in particular of the geometry, more particularly the surface moment of inertia of the cantilever, and also of the mass of the cantilever and the elasticity modulus. The bending curves may be described for example in accordance with beam theory.

[0195] As a result of the surface stresses which are different on the lower side and the upper side of the cantilever, the described deformation or stretching of the cantilever occurs accordingly.

[0196] Via beam theory it is possible for example to predict the point on the deformable part 22, 32 at which the stretching D is the greatest. It is possible to arrange the active transducer 220, 320 at this point in order to obtain an optimal signal-to-noise ratio and in order to respond as sensitively as possible to the stretches. In terms of the precise positioning of the transducers, however, other boundary conditions ought also to be taken into consideration.

[0197] An important part is played in particular by the orientation of the transducers relative to the orientation of the cantilevers. FIG. 2C shows, for example, an undeflected cantilever. When the cantilever comes into contact with the analyte, there is a change in the surface stress and a deformation of the material, as shown in FIG. 2D. In FIG. 2D the cantilever undergoes a deformation perpendicularly to the base 20, or to the bending edge. This is accompanied by a longitudinal stretching DI of the upper surface. At the same time there is a deformation parallel to the base 20, or to the bending edge, which is accompanied by a transverse stretching Dq of the upper surface. With the geometry of the cantilever, it is possible to specify the direction along which a larger stretching D is brought about. The transducer may in particular be oriented along this direction in order to generate a particularly large measurement signal.

[0198] By the overdimensioning of a mechanical stretch at the location of the transducer, the signal emitted by the transducer may be improved still further. Such overdimensioning may be achieved, for example, through the arrangement and shape of the electrodes.

[0199] FIG. 3A shows a further embodiment of the sensor 1. The reference cantilever 3 and the test cantilever 2 in particular have identical geometrical dimensions; more particularly, the height, width and thickness of the reference cantilever 3 correspond to the height, width and thickness of the test cantilever 2. This generates an equal stretching D on the upper surfaces 260, 360. As the geometrical dimensions of the cantilevers 2, 3 are identical, an identical dependency of the measurement signal on the stretching is also expected accordingly.

[0200] The width B of the cantilevers is preferably equal to the height H of the cantilevers 2, 3, thereby enabling a particularly large stretching D on the upper surface 260, 360 of the cantilever 2, 3. In this case, for example, the cantilevers are less than 100 μm wide, less than 100 μm long and less than 1 μm thick, more particularly 50 μm wide, 50 μm long and 0.3 μm thick.

[0201] In the embodiments of the sensor 1 in FIG. 3, the bases 30, 20 of the reference and test cantilevers 3, 2 are also arranged on the same overall base. Accordingly, there is a direct mechanical connection and interaction of the cantilevers via the overall base. This makes it possible for example to reduce the various ambient influences on the cantilevers 2, 3, since the cantilevers 2, 3 can be arranged closer to one another. In particular the bases 30, 20 of the reference and test cantilevers 3, 2 may also be formed in one piece. This ensures that the bases as well have identical material-specific binding properties, and so the measurement outcomes from the passive and active transducers 200, 300, 220, 320 are readily comparable with one another.

[0202] The distance A between the active transducers 320, 220 and the passive transducers 300, 200 is measured along the height direction H of the cantilevers. The distance A is in particular less than 100 μm, which ensures that the transducers are arranged very close to one another, so that, for example spatial ambient influences on the transducers are reduced.

[0203] FIG. 3B shows a further embodiment in which the transducers 200, 220, 300 and 320 are oriented perpendicularly to the base 20, 30. Where with the transverse orientation of the transducer along the bending edge in FIG. 3A a transverse stretching of the cantilevers 22, 32 is measured, a longitudinal stretching of the cantilevers 22, 32 is measured in FIG. 3B.

[0204] FIG. 4 shows a preferred embodiment in this regard, in which the active transducers 320, 220 and the passive transducers 300, 200 lie in each case against the bending edge 10 of the cantilevers 3, 2. With all of the transducers 320, 300, 220, 200 lying against the bending edge 10, the minimum possible distance A between the transducers 320, 300, 220, 200 is realized. Furthermore, in this embodiment, the electrodes 40 and also the transducers 320, 300, 220, 200 are oriented mirror-symmetrically to an axis S of mirror symmetry. In particular the transducers 320, 300, 220, 200 are therefore oriented mirror-symmetrically to one another.

[0205] FIG. 5A shows a further embodiment of the sensor 1. The transducers 300, 320, 200, 220 are contacted via the electrodes 401, 402, 403, 404. In particular the active transducer 220 is connected to the active transducer 320 via the electrode 401. Moreover, the passive transducer 200 is connected to the passive transducer 300 via the electrode 403. The active transducer 220, moreover, is connected to the passive transducer 200 via the electrode 402, whereas the active transducer 320 is connected to the passive transducer 300 via the electrode 404. All in all, therefore, there are four electrodes via which the transducers are electrically contacted with one another. Electrical contacting in this case may be achieved more particularly by applying the transducers to the electrodes, to produce a conductive connection. Since the transducers have a thickness, it may in particular be the case that, on subsequent application of electrodes, no conductive contacting to the electrodes would be achieved at the edges of the transducers. This is ensured only if the thickness of the electrodes is greater than the thickness of the transducers.

[0206] FIG. 5B shows a further embodiment of the sensor 1. The electrodes contacting the transducers 200, 220, 300, 320 have a mirror-symmetrical construction overall. Currents run through the electrodes or voltages are present there, and so, with an asymmetrical design of these electrodes, there may be asymmetrical crosstalk of electrical signals with the other electrodes. This mutual influencing may result in the generation of a control signal between the electrodes, but this may be avoided through the symmetrical construction.

[0207] The transducers 200, 220, 300, 320 are interconnected electrically in particular in what is called a full bridge. The circuit of the full bridge is shown in FIG. 5C. With the full bridge, a DC voltage or AC voltage is applied between the electrodes 403, 401. The passive and active transducers act as voltage dividers between these electrodes, on the basis of their electrical resistances. A full bridge in the form shown has the advantage that no voltage is developed between the electrodes 402, 404 provided the ratio of the resistances of the passive transducer 200 to the active transducer 220 of the test cantilever 2 is equal to the ratio of the resistances of the passive transducer 300 to the active transducer 320 of the reference cantilever 3. All that is needed in order to change the resistance ratios, therefore, is the deviation of one resistance in particular, which is also sufficient to develop a voltage between the electrodes 402, 404 in this way.

[0208] If the reference cantilever 3 and the test cantilever 2 interact with the sample 9 and the analyte 90, then both deformable parts 22, 32 experience, for example, a change in surface stress, which is greater for the deformable part 22 of the test cantilever 2 than for the deformable part 32 of the reference cantilever 3. Accordingly, the resistance of the active test transducer of the deformable part 22 of the test cantilever 2 will vary to a greater extent than for the active reference transducer 320 of the deformable part 32 of the reference cantilever 3. If the resistances of the passive transducers 200, 300 do not change or at least change equally, there is a change in the resistance ratios arising from the deformation of the deformable part 22 of the test cantilever 2 because of the interaction with the analyte 90 of the sample 9, which interacts specifically with the reference layer 24 of the test cantilever 2. In the event of such interaction, accordingly, a voltage is developed between the electrodes 402, 404, and so a force acting on the active test transducer 220 relative to the active reference transducer 320 may be indicated as a transverse bridge voltage VB. The transverse bridge voltage VB preferably scales with the incidence of the analyte 90 in the sample 9, thereby enabling a quantitative evaluation of the measurement signal.

[0209] A transverse bridge voltage detector 44 is able to indicate the transverse bridge voltage VB externally or transmit it, allowing the user of the sensor 1 to see that there is a transverse bridge voltage VB present. In particular, a transverse bridge voltage detector 44 of this kind may also be formed by A/D converter, with the A/D converter converting the transverse bridge voltage VB into a digital signal which can be transmitted to the external measuring apparatus. The A/D converter may be operated in particular in two different measuring modes. The first measuring mode is the differential measuring mode, in which the transverse bridge voltage VB is measured and therefore a relative measurement value for the deformation of the two reference and test cantilevers 3, 2 is generated. In this differential measuring mode, so to speak, the measurement signals of all the transducers 200, 220, 300, 320 are taken into consideration, and so the output signal from the A/D converter is a measurement signal with ambient influences removed, and can be used to derive the relative deformation of the deformable parts 22, 32 and therefore the incidence of an analyte 90.

[0210] The second measuring mode is what is called the absolute measuring mode. In the absolute measuring mode, the transverse bridge voltage is not detected, but instead the signals at the electrodes 402 and 404 respectively are tapped off in isolation from one another, and so it is possible to make a statement regarding the respective deflections of the deformable parts 32, 22. This information remains unavailable to the user in the differential measuring mode.

[0211] FIG. 6 shows a further embodiment of the sensor 1. The sensor 1 in this case comprises multiple cantilever pairs, with each cantilever pair here comprising a reference cantilever 3′ and a test cantilever 2′. The reference cantilever 3′ and test cantilever 2′, or the corresponding transducers, are electrically connected to one another via an electrode circuit, as in FIGS. 5A to C, and consequently it is possible to tap off a transverse bridge voltage VB′ for each cantilever pair. The transverse bridge voltage VW can be tapped off from each cantilever pair by the A/D converter 440, or by the transverse bridge voltage detector 44. In particular in the A/D converter 440, via an A/D converter logic unit, for example, it is possible to output the measurement signal from one particular cantilever pair or to output the integrated measurement signals from all the cantilever pairs, or a combination thereof. It is therefore possible in particular to average the measurement signals over different cantilever pairs, meaning that an incidence of an analyte 90 is indicated with greater statistical significance. It is, however, also possible for different reference layers and receptor layers 34, 24 to be applied on the various cantilever pairs, and so a sensor 1 of this kind enables the sample 9 to be investigated simultaneously for different analytes 90. It is also possible, however, for example, for a single reference cantilever 3 to serve as reference for multiple test cantilevers 2.

[0212] In particular, the sensor 1 may be embodied with the multiplicity of cantilever pairs on a chip 100. A chip here may mean that the sensor 1 has been fabricated from a single substrate, and so, for example, the various cantilevers 2, 3 are mechanically connected to one another. It may also be the case, however, that the chip 100 comprises a further electronic circuit, which is, for example, a CMOS circuit, i.e., a semiconductor circuit that taps off the transverse bridge voltage VB and processes it further directly. A semiconductor circuit of this kind in combination with a sensor is also called a system-on-a-chip.

[0213] FIG. 7 shows schematically the construction of the various deformable parts 22, 32 of the reference and test cantilevers 3, 2, respectively. The construction of the cantilevers is identical except for the receptor layer and the reference layer, respectively, and so interaction with the sample or with the surrounding medium, and also the mechanical design of the cantilever, are very mostly identical.

[0214] On the deformable parts 32, 22 of the reference and test cantilevers 3, 2, respectively, an activation layer 34, 24 is applied. An activation layer 240 is configured to promote adhesion between the surface of the deformable part 32, 22 and a further layer 241, 341. The activation layer 240, furthermore, has the function of producing an asymmetrical layer construction of the cantilever 3, 2, so that there is as large as possible a difference in the stretching of the upper surface of the cantilever and the lower surface of the cantilever. The adhesion promoter layer, or the activation layer 240, may in particular comprise gold or consist of gold.

[0215] Atop the gold layer 240 there may then be a so called self-assembling monolayer 241 applied, which is able to compensate the surface unevennesses of the gold layer and which at the same time provides adhesion promotion for a further layer, specifically the reference and receptor layers 34, 24.

[0216] The construction of the reference layer and the receptor layer 34 and 24, respectively, is different. Both layers, however, are based on a layer which may comprise the so-called protein A 242, which firstly binds to the self-assembling monolayer 241, 341 but also has and is able to bind antibodies 243 or isotype control antibodies 343 on its surface.

[0217] The antibodies 243 are proteins which respond to an antigen 5, or bind to it, and which therefore, in the human immune system, label virus cells, allowing the immune system to destroy the labeled virus accordingly, in order for example to stem or to prevent a viral outbreak. The antibodies 243 are mostly specific to the antigen 5, but may also interact with other, similar antigens 50. FIG. 7 shows that the antibody 243 is able to interact to some extent with the antigen 5 and with the similar antigens 50.

[0218] In contrast to the antibody 243, the isotype control antibody 343 is a protein which preferably does not interact in an ultra-highly specific manner with the antigen 5. As a result, interaction with a specific antigen 5 can be virtually ruled out. This is shown in FIG. 7 by the fact that the isotype control antibody 343 is able to interact only with two similar antigens 50, but not with the antigen 5, shown schematically in square form here. As a result, the relative change in the surface stress of the cantilevers 22, 32 is attributable solely to the specific antigen 5.

[0219] As the test cantilever 2 has an antibody 243 and the reference cantilever 3 has an isotype control antibody 343, it is ensured that in the sample 9, the analyte 90, where the analyte 90 is an antigen 5, is able to interact only with the test cantilever 2. This ensures that the relative deformation of the test cantilever 2 brought about by the analyte, in comparison with the deformation of the reference cantilever 3, is based only on the presence of the analyte 90, or of the antigen 5. Accordingly, with this sensor 1 it is possible to detect an antigen 5 quickly and reliably. In contrast to the upper surface of the cantilevers, the lower surface of the cantilevers is passivated. Such passivation may lead to any interaction, or binding, or absorption or absorption of an analyte 90 from the sample 9 is avoided in or on the cantilever. In particular, however, a passivation layer of this kind also contributes to increasing the asymmetry of the layer construction, in order to maximize the stretching effect at the upper surface of the cantilever 3, 2. The passivation layer may in particular comprise trimethoxysilane and/or a blocking substance.

[0220] The sensor shown may be used in particular to detect the antigens 5 of a Sars-CoV2 virus or of another virus. For this purpose, the receptor layer 24 of the test cantilever 2 comprises, for example, Sars-CoV2 antibodies, whereas the reference layer 34 comprises Sars-CoV2-specific isotype control antibodies. A measurement signal is generated accordingly by the sensor 1 if the antigens 5 of a Sars-CoV2 virus are present in the sample 9 and accumulate at the test cantilever 2 or the receptor layer 24.

[0221] Insofar as is applicable, all individual features represented in the embodiments may be exchanged and/or combined with one another without departing from the scope of the invention.

LIST OF REFERENCE SIGNS

[0222] 1 sensor [0223] 10 bending edge [0224] 2 test cantilever [0225] 20 base [0226] 200 passive test transducer [0227] 22 deformable part [0228] 220 active test transducer [0229] 24 receptor layer [0230] 240 activation layer [0231] 241 self-assembling monolayer [0232] 242 protein A [0233] 243 antibody [0234] 244 passivation layer [0235] 26 surface [0236] 260 upper surface [0237] 262 lower surface [0238] 3 reference cantilever [0239] 30 base [0240] 300 passive reference transducer [0241] 32 deformable part [0242] 320 active reference transducer [0243] 34 reference layer [0244] 340 activation layer [0245] 341 self-assembling monolayer [0246] 342 protein A [0247] 343 isotype control antibody [0248] 344 passivation layer [0249] 36 surface [0250] 360 upper surface [0251] 362 lower surface [0252] 4 electronic unit [0253] 40 electrode [0254] 400, 401, 402, 403 electrodes [0255] 42 transverse bridge voltage detector [0256] 44 AD converter [0257] 440 AD converter logic unit [0258] 5 antigen [0259] 50 similar antigen [0260] 9 sample [0261] 90 analyte [0262] F force [0263] L deflection [0264] D stretching [0265] AT distance between active and passive transducer [0266] AE distance between electrodes [0267] S axis of symmetry [0268] VB transverse bridge voltage